Three-dimensional (3D) tissue culture systems which emulate key physical and molecular features of the extracellular microenvironment, provide tremendous advantages to tissue engineering. An important goal in engineering such materials is the ability to present cell-instructive mechanical and biochemical cues which influence cell fate. Integrins (heterodimeric, transmembrane receptors for extracellular matrix (ECM) proteins) “integrate” mechanochemical information from the ECM with the intracellular environment, activating intracellular signaling cascades which govern many cellular functions, including proliferation, motility, and survival, and thus, are excellent biological targets for manipulating cell fate in 3D culture systems. Typical integrin-targeting gel matrices used for 3D tissue culture incorporate reconstituted matrix proteins such as collagen and hyaluronic acid, all of which have disadvantages associated with protein purification, processing, cost, and poor control over physical properties of the gel. The use of Matrigel (a commercially available, laminin-rich extracellular matrix (ECM)) in 3D tissue modeling, for example in vitro modeling of mammary tumors, also presents numerous challenges, as cell fate in these systems is influenced by a number of undefined, poorly characterized, and highly variable bioactive components. Fully synthetic, bioactive 3D systems incorporating adhesive peptides such as the integrin-binding arginine-glycine-aspartic acid (RGD) sequence found in many ECM proteins, have also been reported, however, these systems lack the complexity of molecular information critical for supporting many cell functions in vitro. Accordingly, development of synthetic biomaterial scaffolds with defined bioactive molecular recognition elements and fine-tunable mechanical properties, offers tremendous advantages to the field of 3D tissue modeling and bioengineering.
Surprisingly, the present invention meets this and other needs. The present invention shows that bioactive hydrogels can be used to culture a number of cognate integrin-expressing tissue types including both normal and malignant human mammary epithelial cells, colon adenocarcinoma, and endothelial cells; and possesses suitable biochemical complexity for eliciting similar morphogenic patterns as those observed in Matrigel, but with the additional advantages of being purely synthetic and void of any animal products, well-characterized and consistent, such that the various molecular elements which influence cell fate can be easily and reproducibly identified.